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Genetic counseling: Opitz BBB - G Syndrome
Opitz BBB - G Syndrome (Opitz Oculo-Geito-Laryngeal Syndrome, Hypertelorism-Hypospadias Syndrome, Opitz-Frias Syndrome) Contracting *Acknowledge prior phone contact *What have you been told about why your were referred to genetics? *What questions or concerns would you like us to address today? *Set agenda for session Genetic Etiology *Genetic heterogeneity **X-linked loci mapping to Xp22.3 and possibly Xq22 ***Only males affected ***Sons of affected males can't be affected, daughters must be carriers ***Women have 50% chance for each pregnancy to inherit the mutation ***Sons of carrier women have 25% chance of being affected **Autosomal dominant inheritance at 22q11.2 *Molecular genetics **Xp22.3 form is caused by mutation in MID1 gene ***Gene product is midin ***Midin is associated with microtubules throughout cell cycle **Xq22 form is caused by mutation in MID2 gene (recently identified) ***Gene structure and protein product almost identical to MID1 ***Expressed in heart, but MID1 is not ***Unsure of clinical implications at this point **Gene on chromosome 22 has not been determined yet *Spontaneous mutations are rare *Almost 100% penetrance Incidence *Over 50 families reported in literature since 1965 *Many families have not been reported Clinical Features *Hypospadias (93%) *Hypertelorsim (91%) *Dysphagia (81%) - may be more common in X-linked form *Developmental delay (43%) *Kidney anomalies (42%) *Laryngotracheal Esophageal cleft (LTE) (38%) *Cleft lip and palate (32%) *Strabismus (28%) *Heart defects (27%) **Patent ductus arteriosus **Atrial septal defect **Conotruncal anomalies *Imperforate anus (21%) - may be more common in X-linked form *Undescended testes (20%) *Hypotonia - usually improves over time *Other characteristic facial findings: **Widow's peak hairline **Ear abnormalities (72%) ***Low set ***Prominent or rotated ears **Broad or flat nose **Small chin *Associated findings **Urinary tract problems **Large fontanels **Underdevelopment of corpus collasum **Lung abnormalities **Lipomas **Diastasis recti *Usually clinically indistinguishable regardless of etiology Natural History **Great variation in range of severity ***Males tend to be more severely affected than females ***Women usually only mildly affected **Rarely symptoms are sever enough to cause death in infancy **Usually normal growth and normal life span Testing **Usually clinical diagnosis is most reliable **Research testing for genes on X chromosome and chromosome 22 ***Mutations have been identified in some families with X-linked Opitz ***If mutation is identified, other at risk relatives can be tested ***Dr. Maximilian Muenke lab offers blood test for changes in MID1 ****Have found changes in 10 of 40 families studied ****Working to find gene on Xq22 **Prenatal diagnosis can be offered once change in MID1 identified ***Polyhydramnios may be sign of affected fetus ***Some features may be observed on level II ultrasound after 22 weeks Surveillance, management, and treatment options **No "treatment" available **Surgical repair of heart defects, hypospadias, imperforate anus, LTE cleft, and some other findings when necessary **OT, PT, and speech therapy when necessary **Children with learning difficulties or mental retardation can obtain special services Differential Diagnosis *FG syndrome *Brachio-skeletal-genital syndrome *Hypospadias and hypertelorism may be isolated or findings in many other syndromes Psychosocial Issues *Guilt *Difficulty dealing with child with many medical issues *Fear of recurrence in future pregnancies *Financial burden *Changes in lifestyle, missed time at work to care for child with medical issues or mental retardation Support/Resources *Pamphlet on Opitz Syndrome :Vanderbilit University Medical Center :DD-2205, MCN, Division of Medical Genetics :Nashville, TN 37232-2578 :Available on line: www.opitznet.org/modopitz.html *Opitz Family Network :PO Box 515 :Grand Lake Colorado 80447 :Phone: 970-627-8935 :Email: opitznet@mac.com :http://gle.egsd.k12.co.us/opitz/index.html *National Organization for Rare Disorders :Phone: 800-999-6673 :http://www.nord-rdb.com/~orphan References *Gorlin RJ, Cohen MM, Hennekam RCM. "Opitz oculo-genito-laryngeal syndrome." Syndromes of the Head and Neck. (2001): 988-990. *Jones KL. "Opitz Syndrome." Smith's Recognizable Patterns of Human Malformation. (1997): 133-135. *Opitz Family Network. (2002) http://gle.egsd.k12.co.us/opitz/index.html Notes The information in this outline was last updated in 2001.